The long term objectives of this project are to continue identifying the immunologic mechanisms responsible for producing immune injury in occupationally related chronic pulmonary diseases. Using an experimental model of hypersensitivity pneumonitis wherein unsensitized animals respond to aerosol inhalation of fungal spores by depressed arterial oxygen tensions and depressed complement levels, observations will be extended to the thermophilic actinomycetes involved in farmer's lung disease. Additional parameters of measurement will include C3 conversion, histamine release from platelets, leukocyte and thrombocyte counts, and clotting time. The endotoxic like properties of these actinomycetes will be compared with and studied biologically by methods used for classical enterobacterial endotoxins. Cotton bract dust (an agent important in byssinosis) aerosols will also be studied for endotoxin properties and in vivo effects following aerosol challenge. The effects of endotoxin on immunization via the aerosol route are planned. It is hypothesized that the endotoxic properties of inhaled particulates initiate inflammation that permits antigens to enter the peripheral circulation and stimulate immune responses, the effectors of which may return to the lung, causing more injury. The inhibitory effects of cortisone, diphenhydramine HCl, and disodium cromoglycate on the responses will be studied to learn more about the mechanisms of pathogenesis and about possible chemotherapeutic approaches. A comparison will be made between the ability of soluble and particulate inhalant antigens to induce cell-mediated immune responses (CMI). Using in vitro correlates of CMI, the local (pulmonary) and systemic immune competence of lymphoid cells from normal animals. An antigen will be prepared in two forms (soluble and insoluble) for aerosol-immunization. It is hypothesized the the physical state of the antigen influences the nature of the immune response generated by the lung and if so, will be of great benefit in understanding the etiology of pulmonary diseases generated by the inhalation of occupational dusts.